In an e-mail Monday to The Associated Press, Cindy Guagenti confirms the 39-year-old actor left Sunday after completing treatment for alcohol and other problems.
He entered an undisclosed rehab center nearly a month ago.
Arquette and Courteney Cox announced their separation in October after 11 years of marriage.
They have a 6-year-old daughter, Coco.
The couple met on the set of the movie "Scream" in 1996 and married three years later.
They are co-starring in the fourth installment of the "Scream" series, due out this year.
Arquette co-starred with Drew Barrymore in the 1999 romantic comedy "Never Been Kissed."